Study shows strong association between treatment with TNF-blocking antibodies and development of serious infections

May 17 2006

A new meta-analysis of many previous studies of TNF- (tumor necrosis factor) blocking antibodies for treatment of rheumatoid arthritis has confirmed a previously discovered increased risk for serious infection and has found that cancer also is a potential risk associated with the drugs.

"This study shows a strong association between treatment with TNF-blocking antibodies and the development of serious infections, such as pneumonia, and cancers," says Eric Matteson, M.D., Mayo Clinic rheumatologist and a senior study investigator. "It's a very serious issue. TNF-blocking antibodies are effective for treatment for rheumatoid arthritis and related conditions, but patients and health care providers must know that there is an increased risk for these complications and be alert for them."

More than half a million patients have received therapy with TNF-blocking antibodies. Patients treated with these drugs usually have not had favorable results with other drug treatments for rheumatoid arthritis or have more severe disease, according to Dr. Matteson. The drugs also are used to treat psoriasis, Crohn's disease and other conditions.

The study involved a systematic literature search for trials of TNF-blocking antibodies for rheumatoid arthritis. In addition, the researchers searched for such trials in the abstract databases of the scientific meetings of the American College of Rheumatology and the European League Against Rheumatism through December 2005 and conducted interviews with the manufacturers of the two licensed TNF-blocking antibodies, infliximab and adalimumab. The investigators found nine trials that met their inclusion criteria, including 3,493 patients who received TNF-blocking antibodies and 1,512 patients who received placebo. They gathered all data related to serious infections and malignancies in the studies' participants. Collectively, using various types of analyses, the researchers found that those treated with TNF-blocking antibodies had 3.3 times the risk of developing cancer than those given placebo, and 2.2 times the risk of serious infection. Cancers were much more common in those patients treated with high doses of TNF-blocking antibodies.

Dr. Matteson explains that TNF-blocking antibodies might be connected with an increased risk for infection and malignancies because the drugs interfere with immunological mechanisms critical to fighting infection and the body's normal function in surveying itself for cancerous cells.

The risk patients undertake when receiving TNF-blocking antibody treatment is "moderate," according to Dr. Matteson. He explains that, on average, rheumatoid arthritis patients are already at twice the risk of serious infections as others, and that taking TNF-blocking antibodies increases that risk.

The decision whether to have TNF-blocking antibody therapy for rheumatoid arthritis must be made by each patient and physician, according to Dr. Matteson. He continues to use this therapy for some patients, he says.

"Most of the patients appropriate for this therapy do not have other good options," he says. "TNF-blocking antibodies are absolutely the best drug for many patients. They have revolutionized the way we treat rheumatoid arthritis, especially in patients who do not respond to conventional therapies. So, I'm not looking to get rid of this therapy. I want to see it used safely."

Dr. Matteson strongly encourages patients who are prescribed TNF-blocking antibodies for rheumatoid arthritis to be especially alert to symptoms of infection, to get their vaccinations, and to undergo cancer screening appropriate for their age and gender.

Tim Bongartz, M.D., Mayo Clinic rheumatology research fellow who led the study, cautions that this study was not a final, overall risk-benefit analysis for TNF-blocking antibodies.

"Even though we detected an increase in malignancies and serious infections, it does not mean that overall the risks outweigh the benefits for patients," he says. "The short duration of trials included in our analysis does not allow any conclusions about the long-term risks of TNF-blocking antibody treatment in rheumatoid arthritis. It may turn out that the sustained beneficial effect of these drugs on patient mobility and general health will have a significant positive impact on the overall survival of patients."

The researchers hope the unique analysis method used in this study can be used in the future to look for rare, negative events during the course of studies of new drugs, so that the public can be alerted to any risks when the drug comes on the market.